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      Drug Design, Development and Therapy (submit here)

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      Pelvic Ultrasound Parameters of Long-Acting Depot Formulation of Leuprorelin in the Treatment of Idiopathic Central Precocious Puberty in Girls

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          Abstract

          Objective

          The present study was designed to compare the changes in ovarian and uterine parameters in girls with idiopathic central precocious puberty (ICPP) before and after gonadotropin-releasing hormone analogues (GnRHa) treatment to determine which sensitive indexes effectively reflect the therapeutic effect.

          Methods

          Sixty girls diagnosed with ICPP were enrolled in the present study. Relevant data were recorded before treatment. Leuprorelin acetate microspheres were injected at a dose of 30–180 μg/(kg four weeks). Relevant parameters were measured and recorded every three months. Changes in each parameter were analyzed to evaluate the clinical effect of leuprorelin in the treatment of girls with ICPP.

          Results

          1) The height grew at a constant rate. 2) The breasts retracted. 3) Changes in pelvic parameters: the volume of the ovary and uterus and major axes of the ovary, uterus, and cervix were reduced; there were no significant changes in vaginal thickness or the uterine fundal–cervical ratio (FCR). 4) Body mass index (BMI) increased.

          Conclusion

          Pelvic ultrasound is helpful in evaluating the efficacy of GnRHA treatment. The changes of ovarian volume and the major axes of the ovary, uterus, cervix can be used as sensitive observation indexes.

          Most cited references12

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          A Critical Appraisal of the Effect of Gonadotropin-Releasing Hormon Analog Treatment on Adult Height of Girls with Central Precocious Puberty

          Abdullah Bereket (2017)
          Central precocious puberty (CPP) is a diagnosis that pediatric endocrinologists worldwide increasingly make in girls of age 6-8 years and is mostly idiopathic. Part of the reason for increasing referral and diagnosis is the perception among the doctors as well as the patients that treatment of CPP with long-acting gonadotropin-releasing hormon analogues (GnRHa) promote height of the child. Although, the timing and the tempo of puberty does influence statural growth and achieved adult height, the extent of this effect is variable depending on several factors and is modest in most cases. Studies investigating GnRHa treatment in girls with idiopathic CPP demonstrate that treatment is able to restore adult height compromised by precocious puberty. However, reports on untreated girls with precocious puberty demonstrate that some of these girls achieve their target height without treatment as well, thus, blurring the net effect of GnRHa treatment on height in girls with CPP. Clinical studies on treatment of girls with idiopathic CPP on adult stature suffers from the solid evidence-base due mainly to the lack of well-designed randomized controlled studies and our insufficiencies of predicting adult height of a child with narrow precision. This is particularly true for girls in whom age of pubertal onset is close to physiological age of puberty, which are the majority of cases treated with GnRHa nowadays. Heterogeneous nature of pubertal tempo (progressive vs. nonprogressive) leading to different height outcomes also complicates the interpretation of the results in both treated and untreated cases. This review will attemp to summarize and critically appraise available data in the field.
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            Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound.

            Valeria Calcaterra, Catherine Klersy, Federica Vinci … (2020)
            Objectives Data on the predictive values of parameters included in the diagnostic work-up for precocious puberty (PP) remain limited. We detected the diagnostic value of basal sex hormone levels, pelvic ultrasound parameters and bone age assessment for activation of the hypothalamic-pituitary-gonadal axis in girls with PP, in order to help in the decision to perform GnRH testing. Patients and methods We retrospectively considered 177 girls with PP. According to puberty evolution, the girls were divided into two groups: rapid progressive central precocious puberty (RP-CPP) and non/slowly progressive/transient forms (SP-PP). In all patients we considered Tanner stage, basal luteinizing hormone (LH) and estradiol (E2) values, bone age, and pelvis examination. We assessed the diagnostic value of each variable and identified the number of pathological parameters that best identify patients with RP-CPP. Results Basal LH ≥ 0.2IU/L, E2 level ≥ 50 pmol/L, uterine longitudinal diameter ≥ 3.5 cm, transverse uterine diameter ≥ 1.5 cm, endometrial echo and ovarian volume ≥ 2 cm3 were significantly associated with RP-CPP (p ≤ 0.01). The ability to diagnose RP-CPP was enhanced with increasing number of pathological hormonal and instrumental parameters (p < 0.001). With more than three parameters detected, sensitivity and specificity reached 58% (95%CI 48-67) and 85% (95%CI 74-92), respectively, with a PPV = 86% (95%CI 76-93) and PPN = 54% (95%CI 43-54); the area under the ROC curve was 0.71 (95%CI 0.65-0.78). Conclusion Despite the availability of different tests, diagnosing RP-CPP remains difficult. A diagnosis model including at least three hormonal and/or ultrasound parameters may serve as a useful preliminary step in selecting patients who require GnRH testing for early detection of RC-PP.
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              The effect of gonadotropin-releasing hormone analog treatment (leuprolide) on body fat distribution in idiopathic central precocious puberty.

              Mehmet Taşcilar, Pelin Bilir, Aysehan Akinci … (2016)
              Gonadotropin-releasing hormone analog (GnRHa) therapy is used in idiopathic central precocious puberty (ICPP) worldwide. It has also been shown that during this therapy, body mass index (BMI) increases slightly as a side effect. We investigated the side effects of GnRHa treatment in ICPP on body composition and insulin resistance (IR). Twenty girls (7.55 +/- 1.02 y) with ICPP were treated with GnRHa (leuprolide) for an average of 20.83 +/- 4.8 months. Bioelectrical Impedance Analysis (BIA) was used to measure the body's fat balance. Nine patients out of 20 (45%) had significant gain weight. We showed a significant elevation in trunk fat mass compare to baseline values (p < 0.01). These nine patients had high homeostasis model assessment (HOMA)-IR and low glucose/insulin (G/I) index. This study showed a slight increase in BMI, moderate increase in total body fat, and exaggerated elevation in trunk fat mass and IR in GnRHa-treated ICPP children.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): dddt
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 07 April 2021
                Publication date Collection: 2021
                Volume: 15
                Pages: 1479-1484
                Affiliations
                [1 ]Child Health Care Department, Baoding Children’s Hospital , Baoding, 071000, Hebei Province, People’s Republic of China
                [2 ]Endocrinology Department, Baoding Children’s Hospital , Baoding, 071000, Hebei Province, People’s Republic of China
                [3 ]Department of Science and Education, Baoding Children’s Hospital , Baoding, 071000, Hebei Province, People’s Republic of China
                Author notes
                Correspondence: Rui-Fang Qi Endocrinology Department, Baoding Children’s Hospital , 3399 North Hengxiang Street, Lianchi District, Baoding City, 071000, Hebei Province, People’s Republic of ChinaTel +86 312 3377 771Fax +86 312 3377 800 Email qiruifang_dr@163.com
                Article
                Publisher ID: 298155
                DOI: 10.2147/DDDT.S298155
                PMC ID: 8039020
                SO-VID: 6c2a66ae-8470-43c5-a125-28bbd374df8a
                Copyright © © 2021 Yang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 18 December 2020
                Date accepted : 16 March 2021
                Page count
                Figures: 0, Tables: 3, References: 12, Pages: 6
                Funding
                Funded by: No external funding;
                No external funding was received to conduct this study.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: leuprorelin microspheres,idiopathic central precocious puberty in girls,pelvic ultrasound,sensitive indicators
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: leuprorelin microspheres, idiopathic central precocious puberty in girls, pelvic ultrasound, sensitive indicators

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